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WO2008157688A3 - Synthèse et utilisation d'analogues de phosphorothioate anti-inverse de la coiffe d'arn messager - Google Patents

Synthèse et utilisation d'analogues de phosphorothioate anti-inverse de la coiffe d'arn messager Download PDF

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Publication number
WO2008157688A3
WO2008157688A3 PCT/US2008/067494 US2008067494W WO2008157688A3 WO 2008157688 A3 WO2008157688 A3 WO 2008157688A3 US 2008067494 W US2008067494 W US 2008067494W WO 2008157688 A3 WO2008157688 A3 WO 2008157688A3
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WO
WIPO (PCT)
Prior art keywords
analogs
arcas
cap
reverse
synthesis
Prior art date
Application number
PCT/US2008/067494
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English (en)
Other versions
WO2008157688A2 (fr
Inventor
Jacek Jemielity
Ewa M Grudzien-Nogalska
Joanna Kowalska
Edward Darzynkiewicz
Robert E Rhoads
Original Assignee
Univ Louisiana State
Jacek Jemielity
Ewa M Grudzien-Nogalska
Joanna Kowalska
Edward Darzynkiewicz
Robert E Rhoads
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to ES08771474.7T priority Critical patent/ES2500515T3/es
Priority to AU2008265683A priority patent/AU2008265683B2/en
Priority to CN200880102959.9A priority patent/CN101855231B/zh
Priority to US12/280,282 priority patent/US8153773B2/en
Priority to SI200831256T priority patent/SI2167523T1/sl
Priority to DK08771474.7T priority patent/DK2167523T3/da
Priority to PL08771474T priority patent/PL2167523T3/pl
Priority to CA2692906A priority patent/CA2692906C/fr
Priority to EP08771474.7A priority patent/EP2167523B1/fr
Priority to EA201070030A priority patent/EA017740B1/ru
Application filed by Univ Louisiana State, Jacek Jemielity, Ewa M Grudzien-Nogalska, Joanna Kowalska, Edward Darzynkiewicz, Robert E Rhoads filed Critical Univ Louisiana State
Publication of WO2008157688A2 publication Critical patent/WO2008157688A2/fr
Publication of WO2008157688A3 publication Critical patent/WO2008157688A3/fr
Priority to HRP20140771AT priority patent/HRP20140771T1/hr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16—Purine radicals
    • C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • C07H19/207—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids the phosphoric or polyphosphoric acids being esterified by a further hydroxylic compound, e.g. flavine adenine dinucleotide or nicotinamide-adenine dinucleotide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P19/00—Preparation of compounds containing saccharide radicals
    • C12P19/26—Preparation of nitrogen-containing carbohydrates
    • C12P19/28—N-glycosides
    • C12P19/30—Nucleotides
    • C12P19/34—Polynucleotides, e.g. nucleic acids, oligoribonucleotides
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P21/00—Preparation of peptides or proteins
    • C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Analytical Chemistry (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Saccharide Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

L'invention concerne de nouveaux analogues de coiffe d'ARN comprenant un ou plusieurs groupes phosphorothioate. Les analogues peuvent également contenir des modifications en position 2'-O de la 7-méthylguanosine qui les empêchent d'être incorporés dans l'orientation inverse pendant une synthèse in vitro de l'ARNm et constituent ainsi des « analogues de coiffe anti-inverse » (ARCA). La modification d'ARCA garantit que l'atome S est positionné précisément dans les sites actifs des protéines de liaison à la coiffe dans la machinerie de traduction et de décoiffage. Les nouveaux analogues S-ARCA sont résistants aux enzymes de décoiffage in vivo. Certains S-ARCA ont une affinité pour eIF4E plus élevée que les analogues correspondants ne contenant pas un groupe phosphorothioate. Lorsque des ARNm contenant divers S-ARCA sont introduits dans des cellules mises en culture, certains sont traduits jusqu'à cinq fois plus efficacement que les ARNm synthétisés avec l'analogue classique m7GpppG.
PCT/US2008/067494 2007-06-19 2008-06-19 Synthèse et utilisation d'analogues de phosphorothioate anti-inverse de la coiffe d'arn messager WO2008157688A2 (fr)

Priority Applications (11)

Application Number Priority Date Filing Date Title
EP08771474.7A EP2167523B1 (fr) 2007-06-19 2008-06-19 Synthèse et utilisation d'analogues de phosphorothioate anti-inverse de la coiffe d'arn messager
CN200880102959.9A CN101855231B (zh) 2007-06-19 2008-06-19 信使rna帽的抗-反向硫代磷酸类似物的合成和用途
US12/280,282 US8153773B2 (en) 2007-06-19 2008-06-19 Synthesis and use of anti-reverse phosphorothioate analogs of the messenger RNA cap
SI200831256T SI2167523T1 (sl) 2007-06-19 2008-06-19 Sinteza in uporaba anti-reverznih fosforotioatnih analogov kape obveščevalne RNA
DK08771474.7T DK2167523T3 (da) 2007-06-19 2008-06-19 Syntese og anvendelse af anti-reverse phosphorothioatanaloger af messenger-rna-cappen
ES08771474.7T ES2500515T3 (es) 2007-06-19 2008-06-19 Síntesis y utilización de análogos de fosforotioato antiinversos de la caperuza de ARN mensajero
CA2692906A CA2692906C (fr) 2007-06-19 2008-06-19 Synthese et utilisation d'analogues de phosphorothioate anti-inverse de la coiffe d'arn messager
PL08771474T PL2167523T3 (pl) 2007-06-19 2008-06-19 Synteza i zastosowanie anty-odwrotnych tiofosforanowych analogów kapu matrycowego RNA
EA201070030A EA017740B1 (ru) 2007-06-19 2008-06-19 Синтез и применение антиинвертированных фосфоротиоатных аналогов кэп-структуры матричной phk
AU2008265683A AU2008265683B2 (en) 2007-06-19 2008-06-19 Synthesis and use of anti-reverse phosphorothioate analogs of the messenger RNA cap
HRP20140771AT HRP20140771T1 (hr) 2007-06-19 2014-08-18 Sinteza i uporaba anti-reverznih analoga fosfortioata na cap glasniäśke rna

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US94484207P 2007-06-19 2007-06-19
US60/944,842 2007-06-19

Publications (2)

Publication Number Publication Date
WO2008157688A2 WO2008157688A2 (fr) 2008-12-24
WO2008157688A3 true WO2008157688A3 (fr) 2009-02-26

Family

ID=40156965

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/067494 WO2008157688A2 (fr) 2007-06-19 2008-06-19 Synthèse et utilisation d'analogues de phosphorothioate anti-inverse de la coiffe d'arn messager

Country Status (15)

Country Link
US (1) US8153773B2 (fr)
EP (1) EP2167523B1 (fr)
CN (3) CN107501370B (fr)
AU (1) AU2008265683B2 (fr)
CA (1) CA2692906C (fr)
CY (1) CY1115525T1 (fr)
DK (1) DK2167523T3 (fr)
EA (1) EA017740B1 (fr)
ES (1) ES2500515T3 (fr)
HK (1) HK1200461A1 (fr)
HR (1) HRP20140771T1 (fr)
PL (1) PL2167523T3 (fr)
PT (1) PT2167523E (fr)
SI (1) SI2167523T1 (fr)
WO (1) WO2008157688A2 (fr)

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US9186372B2 (en) 2011-12-16 2015-11-17 Moderna Therapeutics, Inc. Split dose administration
US9220755B2 (en) 2012-04-02 2015-12-29 Moderna Therapeutics, Inc. Modified polynucleotides for the production of proteins associated with blood and lymphatic disorders
US9572897B2 (en) 2012-04-02 2017-02-21 Modernatx, Inc. Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
US9587003B2 (en) 2012-04-02 2017-03-07 Modernatx, Inc. Modified polynucleotides for the production of oncology-related proteins and peptides

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CA2692906A1 (fr) 2008-12-24
CN107501370A (zh) 2017-12-22
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CN107501370B (zh) 2021-06-18
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US8153773B2 (en) 2012-04-10
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EP2167523A2 (fr) 2010-03-31

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